Chemical mediators and the resolution of airway inflammation.
Asthma pathobiology is remarkable for chronic airway inflammation that fails to spontaneously resolve. No curative therapy is currently available. A growing body of evidence indicates that, in health, inflammation resolution is an active process orchestrated by specific chemical mediators that are elaborated to restore tissue homeostasis. Activated cell membranes release polyunsaturated fatty acids from phospholipids for enzymatic conversion to biologically active mediators with profound regulatory effects on innate and adaptive immunity. Some of these mediators carry anti-inflammatory and pro-resolving actions that are transduced in a cell-type specific manner via specific recognition sites that initiate regulatory intracellular signals, such as presqualene diphosphate remodeling, to limit pro-phlogistic cell activation. Some of these counter-regulatory lipid mediators have been identified in the airway during asthma and defects in their production are associated with disease severity. In this review, we describe the biosynthesis and bioactions of pro-resolving chemical mediators and provide examples of select mediators and their structural analogs with particular relevance to asthma.
Carlo
Troy
T
Brigham and Women's Hospital, Boston, MA, USA.
Levy
Bruce D
BD
D000818:Animals; D032701:Biomimetics / Q000639:trends; D018957:CD59 Antigens / Q000378:metabolism / Q000627:therapeutic use; D004032:Diet; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D005395:Fish Oils / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000276:immunology; D044045:Lipoxins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011106:Polyisoprenyl Phosphates / Q000378:metabolism / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000178:diet therapy / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
D018957:CD59 Antigens; D005395:Fish Oils; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D044045:Lipoxins; D011106:Polyisoprenyl Phosphates; C017672:presqualene pyrophosphate; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid